17-49506485-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002507.4(NGFR):c.395C>T(p.Ser132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,610,500 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (9 hom.)
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54

Genes affected

NGFR (HGNC:7809): (nerve growth factor receptor) Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain. [provided by RefSeq, Jul 2008]

NGFR-AS1 (HGNC:55555): (NGFR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012102872).
• BP6: Variant 17-49506485-C-T is Benign according to our data. Variant chr17-49506485-C-T is described in ClinVar as [Benign]. Clinvar id is 724414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 306 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGFR	NM_002507.4	c.395C>T	p.Ser132Leu	missense_variant	3/6	ENST00000172229.8
NGFR-AS1	NR_103773.1	n.393G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8	c.395C>T	p.Ser132Leu	missense_variant	3/6	1	NM_002507.4	P1
NGFR-AS1	ENST00000514506.1	n.393G>A		non_coding_transcript_exon_variant	3/3	2
NGFR	ENST00000504201.1	c.113C>T	p.Ser38Leu	missense_variant	3/6	2

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 151984 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00275 AC: 654 AN: 237644 Hom.: 5 AF XY: 0.00268 AC XY: 350 AN XY: 130550

Gnomad AFR exome AF: 0.000402

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000561

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.00251

Gnomad OTH exome AF: 0.00304

GnomAD4 exome AF: 0.00187 AC: 2734 AN: 1458398 Hom.: 9 Cov.: 32 AF XY: 0.00178 AC XY: 1289 AN XY: 725618

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000603

Gnomad4 FIN exome AF: 0.0142

Gnomad4 NFE exome AF: 0.00160

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00202 AC: 307 AN: 152102 Hom.: 3 Cov.: 31 AF XY: 0.00269 AC XY: 200 AN XY: 74352

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.000903

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000934 AC: 8

ExAC AF: 0.00277 AC: 334

Asia WGS AF: 0.00145 AC: 5 AN: 3474

EpiCase AF: 0.00191

EpiControl AF: 0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T;.
Eigen	Benign	0.044
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.84	T;T
MetaRNN	Benign	0.012	T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	0.82	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.65	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.97	D;.
Vest4		0.32
MVP		0.83
MPC		0.67
ClinPred		0.015	T
GERP RS		4.4
Varity_R		0.073
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140781803; hg19: chr17-47583847;